Case

A 40-year-old Hispanic female presents to the emergency department with acute right upper quadrant pain that started this morning and has lasted for over 2 hours. She woke up feeling both feverish and nauseous. She noticed it was a continuous sharp, cramping pain and grew more concerned when she urinated and saw her urine was darker than it normally was. The patient also reported vomiting shortly after waking up. The patient denies pain on exertion or shortness of breath. She denies any recent respiratory infections or any extended travel. The patient is otherwise healthy with no significant past medical history. Past surgical history includes an uncomplicated elective C-section two years ago during the birth of her second child. Family history is unremarkable, but the patient does state that her mother had a history of cholelithiasis when she was in her fifties. Her vitals include: height 5’5”, weight: 180 lbs, BMI: 30. Blood pressure 115/80, seated and taken on the right arm. Heart rate: 90 and regular. RR: 18, temperature 99 F. She is awake, alert, and appears in no acute distress. The rest of the physical exam is unremarkable except for pain upon palpation of the right upper quadrant during the abdominal exam.

What is your next step?
1. Imaging of right upper quadrant to confirm suspected diagnosis
2. Laboratory Evaluation (CBC, CMP, AST, ALT, Alk Phos, Bilirubin, B-hCG)

What is the most likely diagnosis?
Bile Duct Obstruction

Background

  • Pathophysiology
      1. A blockage in any pathway that carries bile from the liver to the gallbladder or small intestine that can lead to a buildup of both conjugated and unconjugated bilirubin and alkaline phosphatase
        1. Bile: made of cholesterol, bile salts, and waste products (i.e. bilirubin)
        2. Bile stasis can cause back up into liver and cause obstructive biliary jaundice
      2. Incidence of biliary duct obstruction: 5 cases per 1000 people in the United States
      3. Most common risk factor​—c​holelithiasis
        1. More than 98% of biliary tract disorders are related to gallstones (Ko & Lee, 2002)
        2. Race: higher in Native Americans, Chileans, Asians (i.e. Japan), and Hispanics; least prevalent in African Americans
          1. Native Americans from the Pima tribe have the highest prevalence of cholelithiasis in the United States.
        3. Age: increased risk after age 40, extremely rare in children except in pediatric patients with a hemolytic disorder
        4. Sex: females more likely to be affected than males
        5. Pregnancy
          1. Increased levels of serum estrogens promotes supersaturated cholesterol in bile
          2. Increased serum levels of progesterone may lead to gallbladder stasis, promoting gallstone formation
        6. Oral Contraceptives/Estrogen Replacement Therapy
        7. Family History: significant role in gallstone development, risk greater in female first-degree relatives
        8. Obesity: excess amounts of cholesterol secreted into bile
        9. Rapid Weight Loss: relationship of gallstone formation with low calorie diets not completely understood
          1. Ursodeoxycholic acid (UDCA) prophylaxis has been shown to reduce stone formation during periods of rapid weight loss and has been recommended for use for obese patients who must lose large amounts of weight (Shiffman, Kaplan, Brinkman-Kaplan, & Vickers, 1995)
        10. Diabetes Mellitus: not well understood, but may be related to hepatic insulin resistance (Biddinger et al., 2008) , hypertriglyceridemia, or autonomic neuropathy resulting in biliary stasis
        11. Cirrhosis
        12. Gallbladder Stasis
        13. Drugs
          1. Clofibrate: cholesterol lowering agent; major side effect was production of gallstones
          2. Ceftriaxone: secreted in bile and may precipitate with calcium to form stones
        14. Decreased Physical Activity: associated with risk of symptomatic gallstones
        15. Bacterial Infection: possible relationship between bacteria presence and cholesterol stone formation or foreign bodies enhancing bacterial colonization, promoting existing stone remodeling
      4. What are some other risk factors?
        1. Gastrointestinal: choledocholithiasis, primary sclerosing cholangitis, acute or chronic pancreatitis
        2. Infection: cholangitis, parasitic infections (liver and bile duct worms—flukes)
        3. Oncology: intrinsic or extrinsic tumor compression, lymphoma, pancreatic cancer, biliary cancer (e.g. bile duct cancer)
          1. Malignant obstruction is commonly due to pancreatic carcinoma, cholangiocarcinoma, or metastatic disease. (Tapping, Byass, & Cast, 2011)
        4. Trauma: injury to abdominal area, recent biliary surgery, strictures after invasive procedures
        5. Congenital: choledochal cysts, biliary atresia

  1. Clinical Presentation
    1. Symptoms include:
      1. Right upper quadrant abdominal pain
      2. Dark urine
      3. Fever
      4. Itching
      5. Jaundice
      6. Nausea and vomiting
      7. Pale Colored Stools
    2. What is the differential diagnosis?
      1. Abdominal muscle injury
      2. Acute Coronary Syndrome or atypical MI
      3. Pancreatitis
      4. Acute Mesenteric Ischemia
      5. Congestive Heart Failure with hepatic congestion
      6. Viral or drug-induced hepatitis
      7. Lower Lobe Pneumonia
      8. Pulmonary Embolism
      9. Inflammatory Pleural Effusion
      10. Small bowel obstruction
  2. What are complications of untreated bile duct obstruction?
    1. Life threatening infection or sepsis

Management Principles

  1. Imaging studies used to evaluate a possible bile duct obstruction
    1. Transabdominal Ultrasound
    2. Magnetic Resonance Cholangiopancreatography (MRCP)
    3. Endoscopic Retrograde Cholangiopancreatography (ERCP)
    4. Endoscopic Ultrasonography (EUS)
    5. Intraoperative cholangiography or ultrasonography
    6. Percutaneous Transhepatic Cholangiogram (PTC)
  2. Primary treatment technique in bile duct obstruction
    1. ERCP is the mainstay of treatment as it can be both diagnostic and therapeutic (allows for imaging of the biliary system and intervention to relieve symptoms)
    2. ERCP is widely used as the primary therapy for biliary drainage with a more than 90% success rate (Iwashita, Doi, & Yasuda, 2014)
  3. Interventional radiology procedure: Percutaneous Transhepatic Cholangiography
      1. Introduction
        1. Technique used to visualize the biliary anatomy in the setting of an obstructive jaundice
        2. Rarely utilized as an independent procedure due to the advances of noninvasive imaging modalities that evaluate the biliary tree (MRCP, etc.)
        3. Commonly performed as a component of the percutaneous biliary drainage procedure
      2. Indications
        1. Adjunctive procedure for patients undergoing percutaneous biliary drainage
        2. Suspicion of proximal biliary obstruction where ERCP is unsuccessful
        3. Patients with obstructive jaundice symptoms who are challenging for ERCP (Roux en Y loop patients)
      3. Contraindications/Risk factors
        1. Coagulopathies
          1. The liver is the main production site of many coagulation factors and these may be deranged due to the patient’s biliary problems
          2. Check prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and bleeding time
          3. Correct coagulopathies before proceeding as transhepatic access during the procedure may result in significant bleeding
        2. Ascites
          1. Impedes effective tamponade of blood or bile during procedure
          2. Increased risk of catheter dislodgement and catheter manipulation

            issues

          3. Complete paracentesis before intervention or consider alternative procedure
      4. Steps to perform
        1. Review prior imaging to determine right sided (most common) or left sided approach
        2. Entry is traditionally done “blindly” but ultrasound guidance may be utilized (usually left sided or if prolonged difficulty in finding right sided ducts)
        3. Chiba needle is commonly used to enter below the 10t​h​ rib at the mid-axillary line – this is done to avoid the lung/pleura. Target a dilated bile duct
        4. Use local anesthetic with needle insertion until reaching peritoneum
        5. If right-sided approach advance needle 10-15 cm into the liver. If left-sided approach, or if utilizing ultrasound guidance, advancement of the needle will be under direct ultrasound guidance into a peripheral duct
        6. Remove stylet. Slowly pull Chiba needle back and intermittently inject contrast under fluoroscopy to determine position and gain access to the biliary system
        7. Once inside the biliary tree, slowly inject contrast under continuous fluoroscopy. Oblique images may be performed to fully evaluate the anatomy. (Figure 1)
        8. If only for diagnostic purposes, procedure is complete. Commonly followed with percutaneous biliary drainage (described in next section)
      5. Complications
        1. The major complications of transhepatic cholangiography are sepsis and bleeding.
        2. Serious complications occur in 2% to 8% of cases (Saad, Wallace, Wojak, Kundu, & Cardella, 2010).
      6. Sample imaging

    Bile Duct Obstruction - Figure 1
    Figure 1. The biliary system is accessed and filled with contrast. Fluoroscopic image is remarkable for the valvulae conniventes, suggesting easy filling of the duodenum. Reproduced with permission from Kaiser Permanente, LA.

  4. Interventional radiology procedure: Percutaneous Biliary Drainage
      1. Introduction
        1. Used for difficult biliary obstruction treatment when ERCP fails or is not an option.
        2. Same approach as Percutaneous Transhepatic Cholangiography with addition of drain placement for therapeutic effect.
        3. May be combined with an ERCP for “rendezvous” procedure. This allows for a guidewire to pass from the proximal obstruction percutaneously and past the distal obstruction endoscopically. Used in particularly difficult obstructions which may require device (stent) placement.
      2. Indications
        1. Same as Percutaneous Transhepatic Cholangiography (see previous section)
        2. ERCP fails or is not an option (difficult anatomy, complicated obstruction, proximal biliary tree obstruction that ERCP cannot reach)
      3. Contraindications/Risk factors
        1. Same as Percutaneous Transhepatic Cholangiography (see previous section)
      4. Steps to perform
        1. Entry and access steps are the same as for Percutaneous Transhepatic Cholangiography (see previous section).
        2. Enter bile duct and confirm position via bile backflow or injection of contrast with fluoroscopy visualization.
        3. Exchange entry wire with J-wire and dilate the tract into the duct.
        4. Insert appropriately sized and equipped catheter to cross stricture with help of guidewire. A sample of bile may be taken for analysis at this time. Similarly, a brush biopsy may be performed, but diagnostic yield is low.
        5. Confirm intraluminal and/or enteric position with contrast. As needed exchange wire for heavy duty or super stiff wire for additional support.
        6. Position drainage catheter properly to cover entire lesion. Confirm free drainage of bile through catheter and affix to skin.
      5. Types
        1. External: catheter holes placed upstream from obstruction and bile drains outside the body into external bag (Figure 2)
          1. Effective method for biliary tree decompression, easy to flush and exchange catheter as needed
          2. Least secure type of drainage placement, prone to being pulled out, external drainage bag may inhibit patient’s activities
        2. Internal-external: catheter crosses site of obstruction, catheter holes above and below the obstruction (Figure 3)
          1. Allows for two types of drainage: into external catheter bag or if external portion of catheter is capped diverts bile past obstruction and into distal biliary system
          2. More secure catheter compared to external drain, but may become more frequently occluded
        3. Internal: synthetic stent that crosses biliary obstruction is placed allowing for free flow of bile through to small intestine
          1. Completely internal system, no external drainage bags with risk of dislodgement
          2. Unable to easily resolve device occlusion, cannot deliver additional therapy since catheter access becomes lost
          3. If occlusion present, may need ERCP to replace
      6. Complications
        1. Complications of percutaneous biliary drainage include bleeding, infection, and bile leak (Yee et al., 1987).
        2. The risk of death can range from 0.6-5.6% (Clark, Mitchell, Colley, & Alexander, 1981).
        3. External and Internal-External drains that are hooked up to external drainage bags may lead to imbalance of electrolytes and vitamin absorption due to diversion of natural bile from gastrointestinal system. Check electrolyte status and replenish as needed, bile can be administered orally.
      7. Sample images

    Bile Duct Obstruction - Figure 2
    Figure 2. External biliary drain with pigtail visualized in the common bile duct.

    Bile Duct Obstruction - Figure 3
    Figure 3. External - Internal biliary drain with pigtail formed in the duodenum. Reproduced with permission from Kaiser Permanente, LA.

  5. Additional Interventional Radiology Techniques
    1. Biliary Stenting: see “Types of biliary drainage, Internal” section
      1. Metal stent: longer patency but cannot be easily removed/exchanged. Newer stents are available on the market but with limited data (GORE® Viabil)
      2. Plastic stent: least expensive, high rate of occlusion but can be easily exchanged/removed
    2. Cholecystostomy, Percutaneous Gallbladder Drainage
      1. Allows for quick access and external bile drainage
      2. Commonly performed in critically septic patients with an infected or inflamed gallbladder requiring acute intervention. Patients are usually not surgical candidates at time of procedure
      3. Ultrasound or CT guided transhepatic or transperitoneal approach with external catheter drain placed for drainage

Questions

  1. What is one of the most common causes of malignant bile duct obstruction?
    1. Hepatitis C
    2. Colorectal Cancer in situ
    3. H. Pylori​ infection
    4. Pancreatic carcinoma
    5. MALT Lymphoma
  2. Which of the following is NOT a risk factor for the development of cholelithiasis?
    1. Losing a rapid amount of weight quickly
    2. Being female
    3. Clofibrate use
    4. Native American ancestry
    5. Increased physical activity
  3. A two-day-old infant presents with suspected bile duct obstruction. What congenital condition should be considered as a possible reason for the suspected bile duct obstruction?
    1. Biliary Atresia
    2. Omphalocele
    3. Hirschsprung’s Disease
    4. Primary sclerosing cholangitis
    5. Cholelithiasis
  4. Which of the following obstructive jaundice patients would require percutaneous biliary drainage as a primary intervention?
    1. Distal choledocholithiasis
    2. Sphincter of Oddi dysfunction
    3. Surgical history of Roux-en-Y gastric bypass
    4. Primary sclerosing cholangitis
    5. Acute Pancreatitis

Answers

  1. D
  2. E
  3. A
  4. C

References

  1. Afdhal, N.H. (2011). Diseases of Gallbladder and bile ducts. In: Goldman L, Schafer Al, eds. Goldman’s Cecil Medicine. ​24t​h​ ed. Philadelphia, PA : Saunders Elsevier.
  2. Biddinger, S. B., Haas, J.T., Yu, B.B., Bezy, O., Jing, E., Zhang, W., ... Kahn, C.R. (2009). Hepatic Insulin Resistance Directly Promotes Formation of Cholesterol Gallstones. ​Nature Medicine​. 14 (7): 778-782. doi: 10.1038/nm1785
  3. Clark, R.A., Mitchell, S.E., Colley, D.P., & Alexander, E. (1981). Percutaneous catheter biliary decompression. ​American Journal of Roentgenology​. 137 (3): 503-509. Retrieved from: http://www.ajronline.org/doi/pdf/10.2214/ajr.137.3.503
  4. Iwashita T., Doi S., & Yasuda I. (2014). Endoscopic ultrasound-guided biliary drainage: a review. Clinical journal of gastroenterology​. 7(2): 94-102. ​doi: 10.1007/s12328-014-0467-5
  5. Hahm, J.S., Park, J.Y., Park, K.G., Ahn, Y.H., Lee, M.H., & Park, K.N. (1996). Gallbladder Motility in Diabetes Mellitus Using Real Time Ultrasonography. [Abstract]. American Journal of Gastroenterology. 91 (11): 2391-2394.
  6. Kessel, D., & Robertson, I. (2011). Biliary intervention. ​Interventional Radiology Survival Guide​. 3r​ d​ ed. London, UK: Churchill Livingstone.
  7. Ko, C.W., & Lee, S.P. (2002). Epidemiology and natural history of common bile duct stones and prediction of disease. ​Gastrointestinal Endoscopy, 56 (​ 6), S165-S169. doi:10.1067/mge.2002.129005
  8. Lyon, C. & Clark, D. (2006). Diagnosis of Acute Abdominal Pain in Older Patients. ​American Family Physician. 74​ (9): 1537-1544. Retrieved from: http://www.aafp.org/afp/2006/1101/p1537.html
  9. Rose, S.C. (2012). Biliary System. In ​The Practice of Interventional Radiology. ​1s​ t​ ed. Philadelphia, PA: Saunders.
  10. Saad, W.E.A., Wallace, M.J., Wojak, J.C., Kundu, S. & Cardella, J.F. (2010). Quality Improvement Guidelines for Percutaneous Transhepatic Cholangiography, Biliary Drainage, and Percutaneous Cholecystostomy. ​Journal of Vascular and Interventional Radiology​. 21: 789-795. doi: 10.1016/j.jvir.2010.01.012
  11. Sarin, S.K., Negi, V.S., Dewan, R., Sasan, S., & Saraya, A. (1995). High Familial Prevalence of Gallstones in the First-Degree Relatives of Gallstone Patients. Hepatology​. 22(1):138-141. doi: 10.1002/hep.1840220122
  12. Shiffman, M.L., Kaplan, G.D., Brinkman-Kaplan, V., & Vickers, F.F. (1995). Prophylaxis against Gallstone Formation with Ursodeoxycholic Acid in Patients Participating in a Very-Low-Calorie Diet Program. ​Annals of Internal Medicine​. 122 (12): 899-905. doi:10.7326/0003-4819-122-12-199506150-00002
  13. Stahlberg, D., Reihner, E., Rudling, M., Berglund, L., Einarrson, K. & Angelin, B (1995). Influence of Bezafibrate on hepatic cholesterol metabolism in gallstone patients: Reduced activity of cholesterol 7α-hydroxylase.​ Hepatology​. 21 (4): 1025-1030. DOI: 10.1002/hep.1840210421
  14. Tapping C., Byass O., & Cast J. (2011). Percutaneous transhepatic biliary drainage (PTBD) with or without stenting-complications, re-stent rate and a new risk stratification score. ​European radiology​. ​21​(9):1948-55. doi: 10.1007/s00330-011-2121-7
  15. Tazuma, S. (2006). Epidemiology, pathogenesis, and classification of biliary stones (common bile duct and intrahepatic). ​Gallstone Disease​. ​20​ (6): 1075-1083. doi:10.1016/j.bpg.2006.05.009
  16. Varghese, J.C., Lucey, B.C., & Soto, J.A. (2006). Imaging of Biliary Disorders. In: Medina L, Blackmore C, eds. ​Evidence-Based Imaging Optimizing Imaging in Patient Care.​ New York, NY: Springer Science Business Media.
  17. Yee, A.C., & Ho, C.S. (1987). Complications of percutaneous biliary drainage: benign vs malignant disease. ​American Journal of Roentgenology​. 148 (6): 1207-1209. doi: ​10.2214/ajr.148.6.1207
  18. Yoon, P.W., Bresee, J.S., Olney, R.S., James, L.M, & Khoury, M.J. (1997). Epidemiology of biliary atresia: population-based study. ​Pediatrics.​ 99 (3): 376-382. doi: 10.1542/peds.99.3.376